Our previous studies indicate that immunopathologic mechanisms are responsible for the corneal inflammation in herpes simplex virus (HSV) stromal keratitis. Our further objectives are to characterize in depth the immunologic response parameter to HSV antigens and to corneal antigens in disciform edema, deep infiltrative stromal keratitis, and in latency and reactivation of HSV keratitis. The rabbit eye model for herpes disciform keratitis and deep stromal keratitis will be utilized for immunologic, pathologic, and virologic studies. In addition, we will explore the inbred guinea pig eye ocular infection model as one for latency, immunological studies, as well as studies involving programmed lymphocytes to manipulate the herpetic responses. The T-cell and B-cell contribution to HSV specific cellular and humoral immune response to HSV antigens and to corneal antigens will be followed sequentially during acute infection, latency, and reactivation with regard to clinical sequelae, severity of infection, viral replication in the cornea, and viral shedding. The effects of immunosuppression using a monoclonal specific rabbit T-cell antibody and using cyclosporin A will be evaluated with respect to: clinical sequelae, cellular and humoral immune responses to HSV antigens and to corneal antigens, clearance of infectious HSV, presence of virus and viral antigens in the stroma, T-cell and B-cell functional responses to mitogens, and specific immune responses to T-dependent and T-independent antigens. Elucidation of the nature and function of the complex interaction between viral antigens and the host response involved in HSV stromal keratitis ad in latency and reactivation will allow identification of the mechanisms of immunopathogenesis of corneal inflammation. This type of information is crucial to the development of new immunoprophylactic treatment approaches that might be developed to manage the host's immune response.